Safety and Efficacy of Co-Administration of Sitagliptin and Metformin in China (MK-0431-121)

A Phase III, Multicenter, Double-Blind, Randomized, Placebo-Controlled Clinical Trial in China to Study the Safety and Efficacy of Co-administration of Sitagliptin and Metformin in Patients With Type 2 Diabetes Mellitus

This study will assess the efficacy and safety of initial treatment with sitagliptin and metformin in patients with type 2 diabetes mellitus in China. The primary hypothesis is that after 24 weeks, initial co-administration treatment with sitagliptin and metformin provided greater reduction in hemoglobin A1C (A1C) compared to initial treatment with sitagliptin alone and with metformin alone.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Sitagliptin 50 mg; Drug: Metformin 500 mg; Drug: Metformin 850 mg; Drug: Sitagliptin 100 mg; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 744
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• has type 2 diabetes mellitus
• is male, a female who cannot have children, or a female who agrees to use birth control during the study
• is not on an antihyperglycemic agent (AHA) (hemoglobin A1c [A1C] 7.5-11.0%) or on oral single AHA (A1C 7.0-10.5%) or low-dose AHA combination therapy (A1C 7.0-10.0%)

Exclusion Criteria:

• Patient has type 1 diabetes mellitus or ketoacidosis
• Patient is taking a dipeptidyl peptidase-4 (DPP-4) inhibitor (such as sitagliptin)
• Patient is on a weight loss program not in the maintenance phase or on a weight loss medication
• Patient has a history of liver disease, heart failure, heart disease, stroke, high blood pressure, blood disorders, or cancer
• Patient is HIV positive
• Patient is pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin 50 mg + metformin 500 mg; Sitagliptin 50 mg and metformin 500 mg twice a day for 24 weeks.	Drug: Sitagliptin 50 mg; Sitagliptin 50 mg tablet twice a day, prior to the morning and evening meal, for 24 weeks.; Other Names: Januvia®, Tesavel®, Xelevia®, Ristaben®; Drug: Metformin 500 mg; Metformin 500 mg tablet twice daily, prior to the morning and evening meal, for 24 weeks.; Other Names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
Experimental: Sitagliptin 50 mg + metformin 850 mg; Sitagliptin 50 mg and metformin 850 mg twice a day for 24 weeks.	Drug: Sitagliptin 50 mg; Sitagliptin 50 mg tablet twice a day, prior to the morning and evening meal, for 24 weeks.; Other Names: Januvia®, Tesavel®, Xelevia®, Ristaben®; Drug: Metformin 850 mg; Metformin 850 mg tablet twice daily, prior to the morning and evening meal, for 24 weeks.; Other Names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
Active Comparator: Metformin 500 mg; Metformin 500 mg twice daily for 24 weeks.	Drug: Metformin 500 mg; Metformin 500 mg tablet twice daily, prior to the morning and evening meal, for 24 weeks.; Other Names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
Active Comparator: Metformin 850 mg; Metformin 850 mg twice daily for 24 weeks.	Drug: Metformin 850 mg; Metformin 850 mg tablet twice daily, prior to the morning and evening meal, for 24 weeks.; Other Names: Fortamet®, Glucophage®, Glucophage® XR, Glumetza®, Riomet®, Metgluco®, Glycoran®
Experimental: Sitagliptin 100 mg; Sitagliptin 100 mg once daily for 24 weeks.	Drug: Sitagliptin 100 mg; Sitagliptin 100 mg once daily for 24 weeks.; Other Names: Januvia®, Tesavel®, Xelevia®, Ristaben®
Placebo Comparator: Placebo; Matching placebo tablets for 24 weeks.	Drug: Placebo; Matching placebo tablets to sitagliptin or metformin for 24 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Hemoglobin A1C (A1C) at Week 24	A1C is measured as percent. Thus, this change from baseline reflects the Week 24 A1C percent minus the Week 0 A1C percent.	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 2-hour Post Meal Glucose (2-h PMG) at Week 24	Change from baseline in 2-h PMG at Week 24 is defined as Week 24 2-h PMG minus Week 0 2-h PMG.	Baseline and Week 24
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24	Change from baseline in FPG at Week 24 is defined as Week 24 FPG minus Week 0 FPG.	Baseline and Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Ji L, Han P, Wang X, Liu J, Zheng S, Jou YM, O'Neill EA, Golm GT, Engel SS, Kaufman KD, Shankar RR. Randomized clinical trial of the safety and efficacy of sitagliptin and metformin co-administered to Chinese patients with type 2 diabetes mellitus. J Diabetes Investig. 2016 Sep;7(5):727-36. doi: 10.1111/jdi.12511. Epub 2016 May 19.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2010
• Primary Completion (Actual): December 24, 2012
• Study Completion (Actual): December 24, 2012

Study Registration Dates

• First Submitted: February 24, 2010
• First Submitted That Met QC Criteria: February 24, 2010
• First Posted (Estimate): February 25, 2010

Study Record Updates

• Last Update Posted (Actual): May 23, 2017
• Last Update Submitted That Met QC Criteria: April 27, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate
• Other Study ID Numbers: 0431-121; 2010_514 (Other Identifier: Merck Registration Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php